Search

In this work, we have analyzed the neuroprotective activity of marrubiin against MPTP-induced Parkinson's disease (PD) in rat brains. MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) a neurotoxin was administered intraperitoneally (i.p.,) to rats and then treated using marrubiin. After marrubiin treatment, rats were trained, and tested for behavioral analyses like cognitive performance, open field test, rotarod test, grip strength test, beam walking test, the status of body weight, and striatal levels of neurotransmitters like dopamine, norepinephrine, serotonin, DOPAC, homovanillic acid, 5-hydroxy indole acetic acid, the status of oxidative stress markers like LPO, protein carbonyl content (PCC), Xanthine oxidase (XO), and status of antioxidant enzyme levels like SOD, CAT, GPX in the striatum and hippocampal tissues, status of neuroinflammatory markers like TNF-α, IL1β, IL-6, and status of histological architecture in brain striatum were also analyzed. All these parameters were significantly (p < 0.05) abnormal in MPTP-induced rats. Marrubiin (MB) treated shows significant (p < 0.05) near normal behavioral restoration in cognitive performance, open field, rotarod, grip strength, and beam walking tests. Furthermore, the status of body weight, and levels of neurotransmitters, were also significantly (p < 0.05) reversed to near normalcy in marrubiin-treated rats. Similarly, oxidative stress, antioxidant enzyme levels in the striatum and hippocampal tissues, TNF-α, IL1β, IL-6 levels, and histological architecture were noted to be restored to near normalcy in marrubiin-treated rats. Collectively, our preliminary results highlight the neuroprotective ability of marrubiin. However, the cellular and biochemical mechanisms of marrubiin's neuroprotective ability have to be studied in detail. [ABSTRACT FROM AUTHOR]

Different forms of HCOOH in the depolymerization system play an important role in governing the monomeric products from lignin. We reported two strategies for the introduction of HCOOH to enrich the monophenols from kraft lignin by microwave‐assisted depolymerization. The reaction of lignin models showed that HCOOH was in favor of the cleavage of C−O bonds (β‐O‐4 typically) and partial C−C bonds (Cα−Cβ). Subsequently, Microwave‐assisted depolymerization of lignin with two strategies was conducted via a designed dynamic vapor flow reaction system. Strategy A with HCOOH as pretreatment solvent showed excellent monophenols enrichment with total mass yields of 193.71 mg/g (lignin basis). Strategy B using HCOOH as reforming solvent vapor significantly increased the monophenols selectivity. It presented unique reforming and upgrading performance by generating catechol (42.59 mg/g, lignin basis) and homovanillic acid (17.58 mg/g, lignin basis). This study provided potential strategies for the efficient conversion of kraft lignin into high‐value platform chemicals. [ABSTRACT FROM AUTHOR]

Background: The causes of functional constipation (FC) in adults are unclear, but changes in the gut microbiome may play an important role. The present study aimed to assess the relationship between urinary metabolites of dopamine and serotonin and some dysbiosis indicators in patients with FC. The study included 40 healthy women and 40 women with FC aged 21–46 years. Methods: Urinary levels of homovanillic acid (HVA), 5-hydoxyindoleacetic acid (5-HIAA), p-hydroxyphenylacetic acid (PhAc), and 3-indoxyl sulfate, as final metabolites of dopamine, serotonin, and indole pathway, respectively, were determined using the LC-Ms/Ms method. However, hydrogen–methane and ammonia breath tests were performed. The GA-map Dysbiosis Test was used to identify and characterize the dysbiosis index (DI). Results: In patients with FC, the DI was significantly higher than in the control group: 4.05 ± 0.53 vs. 1.52 ± 0.81 points (p < 0.001), but the number of many types of bacteria varied among individuals. The levels of HVA were higher, while 5-HIAA levels were lower in patients. Moreover, the HVA/5-HIAA ratio had a positive correlation with DI as well as with the severity of symptoms. Conclusions: In patients with functional constipation, the balance in dopamine and serotonin secretion is disturbed, which is associated with changes in the gut microbiome. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) represents a public health issue with a high mortality rate and severe neurological and psychiatric consequences. Mood and anxiety disorders are some of the most frequently reported. Primary and secondary damage can cause a loss of neurons and glial cells, leading to dysfunction of neuronal circuits, which can induce imbalances in many neurotransmitter systems. Monoaminergic systems, especially the dopaminergic system, are some of the most involved in the pathogenesis of neuropsychiatric and cognitive symptoms after TBI. In this work, we summarize the studies carried out in patients who have suffered TBI and describe alterations in the dopaminergic system, highlighting (1) dysfunction of the dopaminergic neuronal circuits caused by TBI, where modifications are shown in the dopamine transporter (DAT) and alterations in the expression of dopamine receptor 2 (D2R) in brain areas with dopaminergic innervation, thus establishing a hypodopaminergic state and (2) variations in the concentration of dopamine and its metabolites in biological fluids of post-TBI patients, such as elevated dopamine (DA) and alterations in homovanillic acid (HVA). On the other hand, we show a large number of reports of alterations in the dopaminergic system after a TBI in animal models, in which modifications in the levels of DA, DAT, and HVA have been reported, as well as alterations in the expression of tyrosine hydroxylase (TH). We also describe the biological pathways, neuronal circuits, and molecular mechanisms potentially involved in mood and anxiety disorders that occur after TBI and are associated with alterations of the dopaminergic system in clinical studies and animal models. We describe the changes that occur in the clinical picture of post-TBI patients, such as alterations in mood and anxiety associated with DAT activity in the striatum, the relationship between post-TBI major depressive disorders (MDD) with lower availability of the DA receptors D2R and D3R in the caudate and thalamus, as well as a decrease in the volume of the substantia nigra (SN) associated with anxiety symptoms. With these findings, we discuss the possible relationship between the disorders caused by alterations in the dopaminergic system in patients with TBI. [ABSTRACT FROM AUTHOR]

Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for its effects on neurotransmission through modulation of GABAergic and glutamatergic receptors and interaction with the dopamine reuptake transporter. The aim of the present study was to investigate the effects of copper overexposure on the levels of dopamine, noradrenaline, and serotonin, or their main metabolites in rat's striatum extracellular fluid. Copper was injected intraperitoneally using our previously developed model, which ensured striatal overconcentration (2 mg CuCl2/kg for 30 days). Subsequently, extracellular fluid was collected by microdialysis on days 0, 15, and 30. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and noradrenaline (NA) levels were then determined by HPLC coupled with electrochemical detection. We observed a significant increase in the basal levels of DA and HVA after 15 days of treatment (310% and 351%), which was maintained after 30 days (358% and 402%), with no significant changes in the concentrations of 5-HIAA, DOPAC, and NA. Copper overload led to a marked increase in synaptic DA concentration, which could contribute to the psychoneurological alterations and the increased oxidative toxicity observed in Wilson's disease and other copper dysregulation states. [ABSTRACT FROM AUTHOR]

In this study, the influence of different tea extract substrates on the biological activities of kombucha beverages was investigated. The variations in bioactive compounds such as polyphenols and flavonoids and their potential health-promoting properties represented by antioxidant activity were analyzed. Our findings shed light on the diverse effects of tea substrates on the production of bioactive compounds and their subsequent impact on the biological activities of kombucha, providing valuable insights for optimizing kombucha production and its potential health benefits. The new tea substrate for kombucha, called horchata, an Ecuadorian tea, shows a similar trend but with a low content of phenolics (4.511 ± 0.111 mg gallic acid equivalent (GAE)/g dry weight (DW)) and flavonoids (1.902 ± 0.0455 mg quercetin equivalent (QE)/g DW), and antioxidant activity (DPPH—33.569 ± 1.377 µmol TROLOX/g DW, ABTS—20.898 ± 2.709 µmol TROLOX/g DW, FRAP—34.456 ± 2.0618 Fe2+ mM/100 g DW compared to black and green tea as substrates for kombucha. Through HPLC-DAD, several polyphenols were registered, and homovanillic acid showed the highest concentration (74.45 mg/100 g). Horchata kombucha scored the highest in sweetness and smell, reflecting its popularity among the tasters, making it a valuable candidate as a kombucha substrate. [ABSTRACT FROM AUTHOR]

Inflammation acts as a dual role in disease initiation and progression, while Cannabis sativa L. (hemp) seeds, known for their abundance of anti-inflammatory phytochemicals, present a promising food source. Additionally, fermentation may optimize the food matrix, thereby augmenting its developmental prospects. This study explores the anti-inflammatory potential of hemp seeds fermented with 10 different probiotic strains. Among these, Lactiplantibacillus plantarum fermented hemp seeds (FHS) demonstrated a significant anti-inflammatory ability, accompanied by a reduction in the expression of critical inflammatory markers such as TLR4, NF-κBp65, and iNOS. Moreover, there is a noteworthy dose-dependent inhibition of inflammatory cytokines TNF-α, IL-6, IL-1β, and NO within a concentration range of 50 to 500 µg/mL. Subsequently, metabolomics analysis using UHPLC-QTOF-MS highlighted significant metabolic alterations in FHS compared to raw hemp seeds (RHS). Through multivariate, univariate, and correlation analyses, indolelactic acid (IA) and homovanillic acid (HVA) emerged as the main anti-inflammatory metabolites in FHS. Validation via HPLC confirmed the concentration of IA and HVA in RHS and FHS and both organic acids demonstrated lower IC50 values for TNF-α, IL-1β, IL-6, IL-18, and NO inhibition, showcasing their potent anti-inflammatory abilities. Furthermore, in vitro gastro-intestinal digestion coupled with the Caco-2 cell monolayer model validates the uptake and bioaccessibility of FHS, further affirming IA and HVA as major anti-inflammatory compounds. Overall, this research sets the stage for the development of novel hemp seed-based products targeting inflammation-associated disorders. [ABSTRACT FROM AUTHOR]

Lactoperoxidase (LPO) is a crucial enzyme found in milk, tears, and saliva, protecting newborns from harmful microorganisms. This study examined the effects of phenolic substances (naringin, morin, esculin, homovanillic acid, and phloridzin) on purified LPO. LPO was purified from bovine milk using affinity chromatography, yielding 66.6 % with a purity of 387.5‐fold. Three methodologies were employed to assess inhibitory properties: spectrophotometric techniques, molecular docking, and MM‐GBSA. The compounds′ IC50 values were 0.0024 μM, 0.0315 μM, 0.0373 μM, 0.0506 μM, and 0.0221 μM, while their Ki values were 0.0059±0.0012 μM, 0.0672±0.0247 μM, 0.0973±0.0369 μM, 0.0664±0.0190 μM, and 0.0470±0.0159 μM, respectively. Naringin exhibited the most potent inhibitory effect, competitively inhibiting LPO. Therefore, naringin could serve as a novel reversible LPO inhibitor. [ABSTRACT FROM AUTHOR]

Despite the advent of combination anti‐retroviral therapy (cART), nearly half of people infected with HIV treated with cART still exhibit HIV‐associated neurocognitive disorders (HAND). HAND can be worsened by co‐morbid opioid use disorder. The basal ganglia are particularly vulnerable to HIV‐1 and exhibit higher viral loads and more severe pathology, which can be exacerbated by co‐exposure to opioids. Evidence suggests that dopaminergic neurotransmission is disrupted by HIV exposure, however, little is known about whether co‐exposure to opioids may alter neurotransmitter levels in the striatum and if this in turn influences behavior. Therefore, we assayed motor, anxiety‐like, novelty‐seeking, exploratory, and social behaviors, and levels of monoamines and their metabolites following 2 weeks and 2 months of Tat and/or morphine exposure in transgenic mice. Morphine decreased dopamine levels, but significantly elevated norepinephrine, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5‐hydroxyindoleacetic acid, which typically correlated with increased locomotor behavior. The combination of Tat and morphine altered dopamine, DOPAC, and HVA concentrations differently depending on the neurotransmitter/metabolite and duration of exposure but did not affect the numbers of tyrosine hydroxylase‐positive neurons in the mesencephalon. Tat exposure increased the latency to interact with novel conspecifics, but not other novel objects, suggesting the viral protein inhibits exploratory behavior initiation in a context‐dependent manner. By contrast, and consistent with prior findings that opioid misuse can increase novelty‐seeking behavior, morphine exposure increased the time spent exploring a novel environment. Finally, Tat and morphine interacted to affect locomotor activity in a time‐dependent manner, while grip strength and rotarod performance were unaffected. Together, our results provide novel insight into the unique effects of HIV‐1 Tat and morphine on monoamine neurochemistry that may underlie their divergent effects on motor and exploratory behavior. [ABSTRACT FROM AUTHOR]

Fermentation is considered an effective tool for improving the functional characteristics of food. In this study, Lacticaseibacillus casei YQ336 was used to ferment yellow whey, and physical and chemical analysis was performed to identify the changes in the nutritional components and antioxidant activity of the fermented yellow whey. Non-targeted metabolomics was used to study the transformation of small molecular substances in the fermented yellow whey. After 48 h of pure culture fermentation with L. casei YQ336, the pH of yellow whey decreased significantly (p < 0.05). Meanwhile, the content of total acids, organic acids, sugars, total phenols, and total flavonoids and the antioxidant activity showed a significant increase (p < 0.05). A total of 628 differential metabolites were identified between fermented and unfermented yellow whey samples, of which 293 were upregulated and 335 were downregulated. After fermentation, due to the growth and metabolic activity of L. casei YQ336, meaningful metabolites such as homovanillic acid, lactic acid, oxalic acid, L-glutamic acid, and phenylalanine, as well as phenyllactic acid, gallic acid, and genistein were produced. This increased the organic acid content and antioxidant activity of yellow whey. The findings provide a theoretical and practical basis for further research on the bio-functional activity of yellow whey and the recycling and utilization of food by-products. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neuroprogressive disorder characterized by loss of dopaminergic neurons in substantia nigra pars compacta. Empagliflozin (EMPA), a SGLT-2 inhibitor, is an oral hypoglycemic agent with reported anti-inflammatory and antioxidant effects. The current study aimed to evaluate the neuroprotective effect of EMPA in rotenone-induced Parkinson's disease. Rats were randomly distributed among five groups as follows: control, rotenone (2 mg/kg), rotenone + EMPA (10 mg/kg), rotenone + EMPA (20 mg/kg), and EMPA (20 mg/kg) groups. They were treated for 30 consecutive days. Rotenone reduced locomotor activity and retention time on the rotarod performance test while elongated descent latency time. On the other side, EMPA corrected these behavioral changes. These results were confirmed by histological examination and number of intact neurons. Moreover, rotenone induced alpha-synuclein accumulation, reduced tyrosine hydroxylase expression, dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid concentrations. On the other side, EMPA reversed such effects induced by rotenone. Depending on previous results, EMPA (20 mg/kg) was selected for further mechanistic studies. Rotenone ameliorated superoxide dismutase and catalase activities and enhanced lipid peroxidation, interleukin-1β, and tumor necrosis factor-α levels. By contrast, EMPA opposed rotenone-induced effects on oxidative stress and inflammation. Besides, rotenone reduced the expression of pAMP-activated protein kinase (pAMPK), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), and Sirtuin-1 (SIRT-1), as well as abrogated NAD+/NADH ratio. However, EMPA activated the AMPK/SIRT-1/PGC-1α pathway. Moreover, rotenone hindered the wnt/β-catenin pathway by reducing the wnt-3a level and β-catenin expression. On the other side, EMPA triggered activation of the wnt/β-catenin pathway. Collectively, EMPA may provide a promising solution for Parkinson's patients worldwide. [ABSTRACT FROM AUTHOR]

This review highlights the advantages of high-precision liquid chromatography with an electrochemical detector (HPLC-ECD) in detecting and quantifying biological samples obtained through intracerebral microdialysis, specifically the serotonergic and dopaminergic systems: Serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), 3-metoxytryptamin (3-MT) and homovanillic acid (HVA). Recognized for its speed and selectivity, HPLC enables direct analysis of intracerebral microdialysis samples without complex derivatization. Various chromatographic methods, including reverse phase (RP), are explored for neurotransmitters (NTs) and metabolites separation. Electrochemical detector (ECD), particularly with glassy carbon (GC) electrodes, is emphasized for its simplicity and sensitivity, aimed at enhancing reproducibility through optimization strategies such as modified electrode materials. This paper underscores the determination of limits of detection (LOD) and quantification (LOQ) and the linear range (L.R.) showcasing the potential for real-time monitoring of compounds concentrations. A non-exhaustive compilation of literature values for LOD, LOQ, and L.R. from recent publications is included. [ABSTRACT FROM AUTHOR]

Objective This study aimed to seek a new method of evaluation and surrogate markers for diffuse neuropsychiatric SLE (NPSLE). Methods We enrolled 44 patients with SLE between 2017 and 2020 who fulfilled at least one of three specific inclusion criteria: high disease activity, abnormal findings (cerebrospinal fluid [CSF] examination, brain MRI, or electroencephalography), or history of neuropsychiatric illness. Psychiatric symptom rating scales (PSYRATS) were evaluated retrospectively. The primary end point was the PSYRATS positivity rate in SLE patients who had not been diagnosed with diffuse NPSLE. Results Based on the 1999 ACR classifications, 7 out of the 44 patients evaluated using PSYRATS had been diagnosed with diffuse NPSLE. PSYRATS positivity was seen in 13 out of 37 SLE patients (35.1%) who had not been diagnosed with diffuse NPSLE, and all these patients were positive for Montgomery–Åsberg Depression Rating Scale (MADRS), an indicator of depression state in PSYRATS. Additionally, in the 20 SLE patients exhibiting depression symptoms who were MADRS-positive, CSF concentrations of the neuroinflammatory markers homovanillic acid (HVA; P  = 0.0400), stromal cell-derived factor-1α (SDF-1α; P  = 0.0431) and stem cell growth factor-β (SCGF-1β; P  = 0.0061) were significantly reduced compared with the 24 MADRS-negative SLE patients, and the levels of HVA, SDF-1α and SCGF-1β correlated with one another (P  < 0.05). Conclusion Many patients with active SLE have subclinical depression, and MADRS evaluation of neuropsychiatric symptoms is useful for detecting them. Additionally, the decrease in CSF levels of HVA, SDF-1 α and SCGF-1β reflects the same pathology, and these may serve as surrogate markers. [ABSTRACT FROM AUTHOR]

Dopamine (DA) is a vital neurotransmitter for brain functions, including pleasure, memory, motivation, and movement control. Dopaminergic neuron degradation is correlated to neurological disorders such as Parkinson's disease, and changes in DA concentration are related to mental health disorders. Currently, the gold standard for monitoring DA concentrations in the brain is electrochemistry. However, although electrochemistry has high sensitivity, it has low specificity for molecules with similar molecular structures, such as DA and its metabolites. Here, we demonstrate that surface‐enhanced Raman spectroscopy (SERS), a vibrational spectroscopy that provides molecule‐specific information with excellent sensitivity, requires small sample sizes/volumes, and is non‐destructive, is optimal for the detection and differentiation of DA and its metabolites. We show that SERS combined with multivariate analysis allows for the detection and differentiation of DA and its metabolites, including 3‐O‐methyldopamine (3‐OMD), homovanillic acid (HVA), 3,4‐dihydroxyphenylacetic acid (DOPAC), and 3‐methoxytyramine (3‐MT) at physiologically relevant concentrations in artificial cerebrospinal fluid (aCSF). [ABSTRACT FROM AUTHOR]

Catecholamines are produced by the sympathetic nervous system or by the medullary adrenal glands and play a key role both as hormones and as neurotransmitters. An increase in their production can lead to hypertension, due to neuroendocrine tumors like pheochromocytoma, paraganglioma and neuroblastoma. Among tumors of neuroendocrine derivation, there are also carcinoids that can cause carcinoid syndrome, associated with an excess of serotonin release. Proper biochemical analysis of patients suffering from these tumors is crucial to confirm the presence of excess production of catecholamines or serotonin and their metabolites. Serious and life-threatening cardiovascular complications related to cathecolamines and their metabolites pose a challenge to the laboratory for a timely and accurate diagnosis of neuroendocrine tumors. The application of innovative technologies to determine these analytes, such as LC-MS/MS, potentially associated with a metabolomic approach, may provide an efficient tool to help physicians recognizing and appropriately treating these still difficult-to-find clinical entities. As a complement to this paper, we present a personal experience about the analysis of biogenic amines and their metabolites performed on both 24-hour and spot urines. The LC-MS/MS method is used with three different preparation phases: total metanephrines (free and conjugate), catecholamines, free methanephrine and serotonin and vanillylmandelic acid (VMA), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA). The organization of the chromatography and mass spectrometry division, based on expert technicians, includes centralized acceptance of samples, automation of the preparation phase and middleware-based validation of the results, offering to clinicians a valuable help in this challenging diagnostic. [ABSTRACT FROM AUTHOR]

Depression is a common illness in people with HIV (PWH) and is associated with substantial morbidity and mortality. The mechanisms that underpin depression in PWH remain incompletely elucidated, and more research is therefore needed to develop effective treatments. One hypothesis is that neurotransmitter levels may be altered. These levels could be influenced by the chronic inflammation and viral persistence that occurs in PWH. We examined a panel of cerebrospinal fluid (CSF) neurotransmitters in PWH on suppressive antiretroviral therapy (ART), many of whom had a current depression diagnosis. CSF monoamine neurotransmitters and their metabolites were measured from participants in studies at the Emory Center for AIDS Research (CFAR). Only participants on stable ART with suppressed HIV RNA from both plasma and CSF were analyzed. Neurotransmitter levels were measured with high-performance liquid chromatography (HPLC). Neurotransmitters and their metabolites included dopamine (DA), homovanillic acid (HVA, a major metabolite of dopamine), serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA, a major metabolite of serotonin), and 4-hydroxy-3-methoxyphenylglycol (MHPG, a major metabolite of norepinephrine). Multivariable logistic regression was used to evaluate factors associated with depression. There were 79 PWH with plasma and CSF HIV RNA levels < 200 copies/mL at the time of the visit, and 25 (31.6%) carried a current diagnosis of depression. Participants with depression were significantly older (median age 53 years versus 47 years, P = 0.014) and were significantly less likely to be African American (48.0% versus 77.8%, P = 0.008). Participants with depression had significantly lower dopamine levels (median 0.49 ng/mL versus 0.62 ng/mL, P = 0.03) and significantly lower 5-HIAA levels (median 12.57 ng/mL versus 15.41 ng/mL, P = 0.015). Dopamine and 5-HIAA were highly correlated. In the multivariable logistic regression models, lower 5-HIAA was significantly associated with the depression diagnosis when accounting for other significant demographic factors. The associations between lower 5-HIAA, lower dopamine, and depression in PWH suggest that altered neurotransmission may contribute to these comorbid conditions. However, the effects of antidepressants on neurotransmitters cannot be ruled out as a factor in the 5-HIAA results. [ABSTRACT FROM AUTHOR]

Biallelic SHQ1 variant-related neurodevelopmental disorder is extremely rare. To date, only six affected individuals, from four families, have been reported. Here, we report eight individuals, from seven unrelated families, who exhibited neurodevelopmental disorder and/or dystonia, received whole-genome sequencing, and had inherited biallelic SHQ1 variants. The median age at disease onset was 3.5 months old. All eight individuals exhibited normal eye contact, profound hypotonia, paroxysmal dystonia, and brisk deep tendon reflexes at the first visit. Varying degrees of autonomic dysfunction were observed. One individual had cerebellar atrophy at the initial neuroimaging study, however, three individuals showed cerebellar atrophy at follow-up. Seven individuals who underwent cerebral spinal fluid analysis all had a low level of homovanillic acid in neurotransmitter metabolites. Four individuals who received 99mTc-TRODAT-1 scan had moderate to severe decreased uptake of dopamine in the striatum. Four novel SHQ1 variants in 16 alleles were identified: 9 alleles (56%) were c.997C > G (p.L333V); 4 (25%) were c.195T > A (p.Y65X); 2 (13%) were c.812T > A (p.V271E); and 1 (6%) was c.146T > C (p.L49S). The four novel SHQ1 variants transfected into human SH-SY5Y neuronal cells resulted in a retardation in neuronal migration, suggestive of SHQ1 variant correlated with neurodevelopmental disorders. During the follow-up period, five individuals still exhibited hypotonia and paroxysmal dystonia; two showed dystonia; and one had hypotonia only. The complex interactions among movement disorders, dopaminergic pathways, and the neuroanatomic circuit needs further study to clarify the roles of the SHQ1 gene and protein in neurodevelopment. [ABSTRACT FROM AUTHOR]

Introduction: Neuroblastoma is the most common extracranial pediatric tumor, accounting for 5–8% of all childhood cancers. Neuroblastomas arise from catecholamine‐secreting neural crest cells and their metabolites, vanillylmandelic acid and homovanillic acid, that are readily detected in urine. Although rarely seen in clinical practice, case reports exist documenting severe intraoperative hypertension. However, data on the incidence of intraoperative hypertension are lacking. Methods: This report is a single‐center retrospective review of patients with neuroblastoma who underwent surgical resection (n = 102) at Boston Children's Hospital from July 1, 2012 to February 28, 2021. Significant intraoperative hypertension was defined as maximum systolic blood pressure greater than 95th percentile +12 mmHg based on normative blood pressure data. Statistical analysis was performed using Fisher's exact test, Wilcoxon rank‐sum test, and logistic regression. Results: The overall incidence of intraoperative hypertension was 13% (n = 13/102). Higher American Society of Anesthesiologists (ASA) physical status was associated with intraoperative hypertension. Antihypertensive medications were administered intraoperatively in 9% of cases (n = 9), and the use was significantly associated with intraoperative hypertension. Of patients with preoperative urine catecholamine data (n = 82), all 10 patients who had intraoperative hypertension were noted to have elevated preoperative urine catecholamines. Intraoperative hypertension was not associated with postoperative hypertension, postoperative hypotension, or increased intensive care unit length of stay. Discussion/Conclusion: Intraoperative hypertension in patients with neuroblastoma remains a relatively uncommon occurrence; however, it does occur at a frequency higher than previously described. While intraoperative hypertension is associated with an increased use of antihypertensive medications in the operating room, it is not associated with adverse perioperative outcomes. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are widely used in the treatment of immune-mediated diseases due to their anti-inflammatory and immunosuppressive effects. Prednisone is one of the most commonly used GCs. However, it is still unknown whether prednisone affects gut fungi in rats. Herein we investigated whether prednisone changed the composition of gut fungi and the interactions between gut mycobiome and bacteriome/fecal metabolome in rats. Twelve male Sprague-Dawley rats were randomly assigned to a control group and a prednisone group which received prednisone daily by gavage for 6 weeks. ITS2 rRNA gene sequencing of fecal samples was performed to identify differentially abundant gut fungi. The associations between gut mycobiome and bacterial genera/fecal metabolites obtained from our previously published study were explored by using Spearman correlation analysis. Our data showed that there were no changes in the richness of gut mycobiome in rats after prednisone treatment, but the diversity increased significantly. The relative abundance of genera Triangularia and Ciliophora decreased significantly. At the species level, the relative abundance of Aspergillus glabripes increased significantly, while Triangularia mangenotii and Ciliophora sp. decreased. In addition, prednisone altered the gut fungi-bacteria interkingdom interactions in rats after prednisone treatment. Additionally, the genus Triangularia was negatively correlated with m-aminobenzoic acid, but positively correlated with hydrocinnamic acid and valeric acid. Ciliophora was negatively correlated with phenylalanine and homovanillic acid, but positively correlated with 2-Phenylpropionate, hydrocinnamic acid, propionic acid, valeric acid, isobutyric acid, and isovaleric acid. In conclusion, long-term prednisone treatment caused fungal microbiota dysbiosis and might alter the ecological interaction between gut mycobiome and bacteriome in rats. [ABSTRACT FROM AUTHOR]

The present study aims to provide information about the antioxidant capacity and secondary metabolites from different plant parts of two species that are grown in Ecuador: Chionanthus pubescens (the Ecuadorian national tree), and Chionanthus virginicus (the fringe tree—endemic to the United States of America and adapted to Ecuador's physiographical and ecological conditions). These two species have still not been investigated for these characteristics. A comparative estimation of the antioxidant activities between the leaf, fruit, and inflorescence extracts was performed. In the quest for new medicines, the extracts were analyzed for phenolic, anthocyanin, and flavonoid content. A slight difference was observed between C. pubescens and C. virginicus flowers, the highest antioxidant activity being found in the C. pubescens leaf (DPPH IC50 = 62.8866 mg/mL, ABTS IC50 = 55.852 mg/mL, and FRAP IC50 = 2.8466 g/mL). Our results showed correlations between antioxidant activity, total phenolic content, and flavonoids. This study confirmed that the C. pubescens leaves and fruits from the Andean region of Ecuador represent a good source of antioxidants, especially due to the presence of a high content of phenolic compounds (homovanillic acid, 3,4 dimethoxyphenylacetic acid, vanillic acid, gallic acid, etc.) as determined by the HPLC-DAD method. [ABSTRACT FROM AUTHOR]

Tetrodotoxin (TTX) inhibits neurotransmission in animals, and there is no specific antidote. In clinical practice in China, Althaea rosea (A. rosea flower) extract has been used to treat TTX poisoning. In this work, the efficacy of the ethyl acetate fraction extract of A. rosea flower in treating TTX poisoning in rats was investigated. A high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed to determine nine neurotransmitters in rat brain tissue, including γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), noradrenaline (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), epinephrine (E), and tyramine (Tyn). The detoxifying effect of A. rosea flower was verified by comparing the changes in neurotransmitters' content in brain tissue before and after poisoning in rats. The assay was performed in multiple reaction monitoring mode. The quantification method was performed by plotting an internal-standard working curve with good linearity (R2 > 0.9941) and sensitivity. Analyte recoveries were 94.04–107.53% (RSD < 4.21%). Results indicated that the levels of 5-HT, DA, E, and NE in the brains of TTX-intoxicated rats decreased, whereas the levels of GABA, Tyn, and 5-HIAA showed an opposite trend, and HVA and DOPAC were not detected. The levels of all seven neurotransmitters returned to normal after the gavage administration of ethyl acetate extract of A. rosea flower to prove that the ethyl acetate extract of A. rosea flower had a therapeutic effect on TTX poisoning. The work provided new ideas for studies on TTX detoxification. [ABSTRACT FROM AUTHOR]

A stopped-flow microfluidic system to monitor glutathione peroxidase (GPx) activity and evaluate potential inhibitors of the enzyme has been developed based on the integration of the microfluidic chip in the reaction/detection zone. This integration supposes the physical alignment at the optimal location of the microfluidic channel, both the magnetically retained enzyme microreactor (MREµR) and the remote luminescence detection using a focused bifurcated fiber optic bundle (BFOB) connected to a conventional spectrofluorometer detector. The method is based on the coupling of two competitive oxidative chemical reactions, in which glutathione (GSH) and homovanillic acid (HVA) competed for their interaction with hydrogen peroxide in the presence of the magnetically retained GPx-MNPs. The biocatalytic reaction was followed by monitoring the fluorescence of the biphenyl-HVA dimer formed. The dynamic range of the calibration graph was 0.45–10 µmol L−1, expressed as GSH concentration with a detection limit of 0.1 µmol L−1 (r2 = 0.9954, n = 10, r = 3). The precision expressed as the relative standard deviation (RSD%) was between 0.5 and 3.9%. The stopped-flow microfluidic system showed a sampling frequency of 25 h−1. The method was applied to the study of GPx inhibition provided by three inhibitory compounds, two metallic ions Hg(II) and Cu(II) and t-butyl hydroperoxide, and their presence in liquid samples, as water, milk, and edible oil. Recovery values between 88.7 and 99.4% were achieved in all instances. [ABSTRACT FROM AUTHOR]

Introduction: Decreased dopaminergic activity – as reflected by lower levels of the major metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) – may be involved in the pathophysiology of attempted suicide. An inverse association has also been found between dopaminergic activity and clinical symptoms of depression and anxiety in non-suicidal individuals. The aim of this study was to assess the relationship between CSF-HVA and clinical symptoms associated with an increased risk of suicide in individuals who attempted suicide. Methods: Ninety-five people (52 women; 43 men) who had recently attempted suicide received lumbar punctures to analyse levels of HVA in the CSF. They were also evaluated with the Comprehensive Psychopathological Rating Scale, from which scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), the Brief Scale of Anxiety (BSA), and an item on suicidal thoughts were analysed. Results: Among female participants, CSF-HVA was significantly and negatively correlated with BSA total scores, after adjusting for covariates (beta = −0.442, p = 0.002), but not with scores on the MADRS or suicidal thought item. No significant correlations were observed between CSF-HVA and symptoms among male participants. Conclusion: Our findings suggest that lower dopaminergic activity may be associated with clinical symptoms of anxiety among women who have recently attempted suicide. [ABSTRACT FROM AUTHOR]

Cyclo-glycylproline (cGP) promotes neurotrophic effects in damaged brains by regulating the bioavailability of insulin-like growth factor-1(IGF-1). However, further studies regarding the ejects of cGP on the intact brain are necessary to establish it as a fimctional food for normal and healthy brains. In this stud% we investigated the efiect of cGP consumption on cognitive functions in healthy htiman& Furthermore, cGP permeability in intact brains and its effects on monoamine release were investigated by conducting cells culture and microdialysis studies in healthy rats. The findings of this open trial of 10 healthy participants revealed that the administration of 150 mg of cGP for 8 weeks improved cognitive function, particularly in terms of attention and language scores. No adverse events related to cGP administration were observed and our results indicate that cGP used at the dose in this study can improve cognitive functions in healthy humans without adverse effects. Good cGP permeability was observed through the blood-brain barrier in the intact cell culture model, and peroral cGP administration increased cGP concentration in the dialysate from the rats5 striatum. Regarding monoamine release, cGP-fed cells in the intact PC12 cell culture exhibited stimulated releases of dopamine, and cGP-administered healthy rats revealed dopamine metabolite (homovanillic acid) upregulation in the striatum. Therefore, cGP is a promising dietary supplement associated with improved cognitive fiinction in healthy humans. Further investigations are required to bridge the gap between cGP intake and dopamine release. [ABSTRACT FROM AUTHOR]

Repeated exposure to low-level blast overpressures can produce biological changes and clinical sequelae that resemble mild traumatic brain injury (TBI). While recent efforts have revealed several protein biomarkers for axonal injury during repetitive blast exposure, this study aims to explore potential small molecule biomarkers of brain injury during repeated blast exposure. This study evaluated a panel of ten small molecule metabolites involved in neurotransmission, oxidative stress, and energy metabolism in the urine and serum of military personnel (n = 27) conducting breacher training with repeated exposure to low-level blasts. The metabolites were analyzed using HPLC—tandem mass spectrometry, and the Wilcoxon signed-rank test was used for statistical analysis to compare the levels of pre-blast and post-blast exposures. Urinary levels of homovanillic acid (p < 0.0001), linoleic acid (p = 0.0030), glutamate (p = 0.0027), and serum N-acetylaspartic acid (p = 0.0006) were found to be significantly altered following repeated blast exposure. Homovanillic acid concentration decreased continuously with subsequent repeat exposure. These results suggest that repeated low-level blast exposures can produce measurable changes in urine and serum metabolites that may aid in identifying individuals at increased risk of sustaining a TBI. Larger clinical studies are needed to extend the generalizability of these findings. [ABSTRACT FROM AUTHOR]

Both cerebrospinal fluid (CSF) homovanillic acid (HVA) and striatal dopamine transporter (DAT) binding on single-photon emission computed tomography (SPECT) reflect nigrostriatal dopaminergic function, but studies on the relationship between the two have been limited. It is also unknown whether the reported variance in striatal DAT binding among diseases reflects the pathophysiology or characteristics of the subjects. We included 70 patients with Parkinson's disease (PD), 12 with progressive supranuclear palsy (PSP), 12 with multiple system atrophy, six with corticobasal syndrome, and nine with Alzheimer's disease as disease control, who underwent both CSF analysis and 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-ioflupane) SPECT. We evaluated the correlation between CSF HVA concentration and the specific binding ratio (SBR) of striatal DAT binding. We also compared the SBR for each diagnosis, controlling for CSF HVA concentration. The correlations between the two were significant in patients with PD (r = 0.34, p = 0.004) and PSP (r = 0.77, p = 0.004). The mean SBR value was the lowest in patients with PSP and was significantly lower in patients with PSP than in those with PD (p = 0.037) after adjusting for CSF HVA concentration. Our study demonstrates that striatal DAT binding correlates with CSF HVA concentration in both PD and PSP, and striatal DAT reduction would be more advanced in PSP than in PD at an equivalent dopamine level. Striatal DAT binding may correlate with dopamine levels in the brain. The pathophysiology of each diagnosis may explain this difference. [ABSTRACT FROM AUTHOR]

Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are diagnostic markers of neuroblastoma. The purpose of this study was to understand the reason for the discrimination of structural analogues (VMA and HVA) onto a graphite electrode coated with an electrochemically oxidized urea derivative. Density functional theory calculations (DFT), FTIR spectroscopic measurements, and electrochemical impedance spectroscopic measurements were used in this work. Density functional theory calculations (DFT) were used to identify the most suitable binding sites of the urea derivative and to describe possible differences in its interaction with the studied analytes. The FTIR measurement indicated the enhancement and disappearance of NH vibrations on graphite and platinum surfaces, respectively, that could be connected to a different orientation and thus provide accessibility of the urea moiety for the discrimination of carboxylates. Additionally, the higher the basicity of the anion, the stronger the hydrogen-bonding interaction with –NH-groups of the urea moiety: VMA (pKb = 10.6, KAds = (5.18 ± 1.95) × 105) and HVA (pKb = 9.6, KAds = (4.78 ± 1.58) × 104). The differential pulse voltammetric method was applied to detect VMA and HVA as individual species and interferents. As individual analytes, both HVA and VMA can be detected at a concentration of 1.99 × 10−5 M (RSD ≤ 0.28, recovery 110–115%). [ABSTRACT FROM AUTHOR]

The incidence of congenital neuroblastoma has increased in the recent years. The purpose of this study was to describe the clinical and biochemical characteristics of cases of congenital neuroblastoma diagnosed in our center. We report three cases of congenital neuroblastoma diagnosed in our hospital. In two, diagnosis was made prenatally, whereas the other case was detected in the immediate neonatal period. In the three cases, neuroblastoma was located in the abdominal region and exhibited elevated concentrations of catecholamines or their metabolites in single voided urine samples. Two tumors were classified as stage M, and one as stage L2. The N-MYC oncogen was not amplified in any of the cases studied. Histopathological analysis was favorable in the three cases. The tumor was resected in two patients. The three received chemotherapy. The measurement of catecholamines and their metabolites is essential in the diagnosis of neuroblastoma. When 24 h urine cannot be collected, single voided urine can be used to calculate the index based on creatinine concentrations. [ABSTRACT FROM AUTHOR]

Thyrotropin-releasing hormone (TRH), at doses lower than those needed to stimulate prolactin secretion directly, can almost completely antagonize dopamine inhibition of prolactin release. In normal men, prolactin increases 15 min following an i. v. bolus of 12.5 µg TRH (the mini-TRH test), but not the maximal prolactin response to TRH or basal prolactin, positively correlated with prolactin response to haloperidol and negatively with 24-h urinary excretion of homovanillic acid (HVA). These results suggest that the mini-TRH test is a better estimate of dopamine inhibition of prolactin release than the maximal prolactin response or basal prolactin level. A recent neuroimaging study suggested that in schizophrenia, there is a widely distributed defect in extrastriatal dopamine release, but the patients were not in the most acute phase of psychosis. The evidence is reviewed that this defect extends to tuberoinfundibular dopamine (TIDA) and which symptoms are associated with the test. In patients with acute nonaffective psychosis, the mini-TRH test positively correlated with nonparanoid delusions and memory dysfunction, indicating decreased dopamine transmission in association with these symptoms. In patients with acute drug-naïve first-episode schizophrenia, the mini-TRH test negatively correlated with negative disorganization symptoms and with basal prolactin. The latter correlation suggests the contribution of factors related to maximal prolactin stimulation by TRH; therefore, an alternative dose of 6.25 μg TRH could be used for the mini-TRH test in first-episode patients, allowed by increased sensitivity of the present prolactin tests. Future studies are needed to investigate whether the mini-TRH test could help in finding the optimal antipsychotic medication. [ABSTRACT FROM AUTHOR]

Objective: Evidence shows that the impairment of executive function (EF) is mainly attributed to the degeneration of frontal-striatal dopamine pathway. Glial cell line-derived neurotrophic factor (GDNF), as the strongest protective neurotrophic factor for dopaminergic neurons (DANs), may play a role in EF to some extent. This study mainly explored the correlation between serum GDNF concentration and EF performance in Parkinson's disease (PD). Methods: This study recruited 45 healthy volunteers (health control, HC) and 105 PD patients, including 44 with mild cognitive impairment (PD-MCI), 20 with dementia (PD-D), and 20 with normal cognitive function (PD-N). Neuropsychological tests were performed to evaluate EF (working memory, inhibitory control, and cognitive flexibility), attention, language, memory, and visuospatial function. All subjects were tested for serum GDNF and homovanillic acid (HVA) levels by ELISA and LC-ESI-MS/MS, respectively. Results: PD-MCI patients showed impairments in the trail making test (TMT) A (TMT-A), TMT-B, clock drawing test (CDT) and semantic fluency test (SFT), whereas PD-D patients performed worse in most EF tests. With the deterioration of cognitive function, the concentration of serum GDNF and HVA in PD patients decreased. In the PD group, the serum GDNF and HVA levels were negatively correlated with TMT-A (rGDNF = -0.304, P < 0.01; rHVA = -0.334, P < 0.01) and TMT-B (rGDNF = -0.329, P < 0.01; rHVA = -0.323, P < 0.01) scores. Serum GDNF levels were positively correlated with auditory verbal learning test (AVLTH) (r = 0.252, P < 0.05) and SFT (r = 0.275, P < 0.05) scores. Serum HVA levels showed a positively correlation with digit span test (DST) (r = 0.277, P < 0.01) scores. Stepwise linear regression analysis suggested that serum GDNF and HVA concentrations and UPDRS-III were the influence factors of TMT-A and TMT-B performances in PD patients. Conclusion: The decrease of serum GDNF concentration in PD patients was associated with impaired inhibitory control, cognitive flexibility, and attention performances. The changes of GDNF and HVA might synergistically participate in the occurrence and development of executive dysfunction in PD patients. [ABSTRACT FROM AUTHOR]

Background: A. chinense frequently used in Miao medicine to treat rheumatic diseases. However, as a famous toxic herb, Alangium chinense and its representative components exhibit ineluctable neurotoxicity, thus creating significant challenges for clinical application. The combined application with compatible herbs in Jin-Gu-Lian formula attenuates such neurotoxicity according to the compatible principle of traditional Chinese medicines. Purpose: We aimed to investigate the detoxification of the compatible herbs in Jin-Gu-Lian formula on A. chinense-induced neurotoxicity and investigate its mechanism. Methods: Neurobehavioral and pathohistological analysis were used to determine the neurotoxicity in rats administered with A. chinense extract (AC), extract of compatible herbs in Jin-Gu-Lian formula (CH) and combination of AC with CH for 14 days. The mechanism underlying the reduction of toxicity by combination with CH was assessed by enzyme-linked immunosorbent assays, spectrophotometric assays, liquid chromatography tandem-mass spectrometry and real-time reverse transcription-quantitative polymerase chain reaction. Results: Compatible herbs attenuated the AC-induced neurotoxicity as evidenced by increased locomotor activity, enhanced grip strength, the decreased frequency of AC-induced morphological damage in neurons, as well as a reduction of neuron-specific enolase (NSE) and neurofilament light chain (NEFL) levels. The combination of AC and CH ameliorated AC-induced oxidative damage by modulating the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). AC treatment significantly reduced the levels of monoamine and acetylcholine neurotransmitters in the brains of rats, including acetylcholine (Ach), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), and serotonin (5-HT). Combined AC and CH treatment regulated the abnormal concentrations and metabolisms of neurotransmitters. Pharmacokinetic studies showed that the co-administration of AC and CH significantly decreased plasma exposure levels of two main components of AC, as evidenced by the reduction of maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC) compared to AC. In addition, the AC-induced downregulation in mRNA expression of cytochrome P450 enzymes was significantly reduced in response to combined AC and CH treatment. Conclusion: Compatible herbs in Jin-Gu-Lian formula alleviated the neurotoxicity induced by A. chinense by ameliorating oxidative damage, preventing abnormality of neurotransmitters and modulating pharmacokinetics. [ABSTRACT FROM AUTHOR]

Glioblastoma is one of the deadliest malignant gliomas. Capsaicin is a homovanillic acid derivative that can show anti-cancer effects by regulating various signaling pathways. The aim of this study is to investigate the effects of capsaicin on cell proliferation via ferroptosis in human U87-MG and U251 glioblastoma cells. Firstly, effects of capsaicin treatment on cell viability were determined by MTT analysis. Next, cellular-proliferation and cytotoxicity assays were determined by analyzing bromodeoxyuridine (BrdU) and lactate dehydrogenase (LDH) activity, respectively. Following, acyl-CoA synthetase long chain family member 4 (ACSL4), glutathione peroxidase 4 (GPx4), 5-hydroxyeicosatetraenoic acid (5-HETE), total oxidant status (TOS), malondialdehyde (MDA), total antioxidant status (TAS) and reduced glutathione (GSH) levels were determined by ELISA. Additionally, ACSL4 and GPx4 mRNA and protein levels were analyzed. Capsaicin showed a concentration-dependent anti-proliferative effects in U87-MG and U251 cells. Cell viability was decreased in the both cell lines treated with capsaicin concentrations above 50 μM, while LDH activity increased. Treatment of 121.6, 188.5, and 237.2 μM capsaicin concentrations for 24 h indicated an increase in ACSL4, 5-HETE, TOS and MDA levels in U87-MG and U251 cells (p < 0.05). On the other hand, we found that capsaicin administration caused a decrease in BrdU, GPx4, TAS and GSH levels in U87-MG and U251 cells (p < 0.05). Besides, ACSL4 mRNA and protein levels were increased in the glioblastoma cells treated with capsaicin, whereas GPx4 mRNA and protein levels were decreased. Finally, capsaicin might be used as a potential anticancer agent with ferroptosis-induced anti-proliferative effects in the treatment of human glioblastoma. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs), such as imidazoles, can be used to prevent the sorption of analytes onto the walls of the capillary. Prior works have confirmed that coating the capillary wall with a cationic layer can increase its surface stability, thereby improving the repeatability of the separation process. In this study, micellar electrokinetic chromatography (MEKC) is employed to evaluate how two ILs with different anions—namely, 1-hexyl-3-methylimidazolium chloride [HMIM+Cl−] and 1-hexyl-3-methylimidazolium tetrafluoroborate [HMIM+BF4−]—affect the separation efficiency for biogenic amines (BAs) such as metanephrine (M), normetanephrine (NM), vanilmandelic acid (VMA), and homovanillic acid (HVA) in urine samples. To this end, solid-phase extraction (SPE) is employed using different sample pH values, with the results demonstrating that HVA and VMA is easily extracted at a sample pH of 5.5, while a sample pH of 9.0 facilitated the extraction of M and NM. In the applied SPE protocol, selected analytes were isolated from urine samples using hydrophilic–lipophilic-balanced (HLB) columns and eluted with methanol (MeOH). The validation data confirmed the method's linearity (R2 > 0.996) for all analytes within the range of 0.25–10 µg/mL. The applicability of the optimized SPE-MEKC-UV method was confirmed by employing it to quantify clinically relevant BAs in real urine samples from pediatric neuroblastoma (NBL) patients. [ABSTRACT FROM AUTHOR]

Table olives and olive oils are the main dietary sources of hydroxytyrosol (HT), a natural antioxidant compound that has emerged as a potential aid in protection against cardiovascular risk. Bioavailability studies with olive oils showed that HT is bioavailable from its free form and from conjugated forms such as oleuropein and its aglycone. Still, its low dietary intake, poor bioavailability, and high inter-individual variability after absorption through the gastrointestinal tract hamper its full benefits. In a randomized, controlled, blinded, cross-over study, we investigated the impact of HT metabolism and bioavailability by comparing two olive-derived watery supplements containing different doses of HT (30.58 and 61.48 mg of HT/dosage). Additionally, HT-fortified olive oil was used in the control group. To this aim, plasma and urine samples were evaluated in 12 healthy volunteers following the intake of a single dose of the supplements or fortified olive oil. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h after intake. HT and its metabolites were analyzed using UHPLC-DAD-MS/MS. Pharmacokinetic results showed that dietary HT administered through the food supplements is bioavailable and bioavailability increases with the administered dose. After intake, homovanillic acid, HT-3-O-sulphate, and 3,4-dihydroxyphenylacetic acid are the main metabolites found both in plasma and urine. The maximum concentrations in plasma peaked 30 min after intake. As bioavailability of a compound is a fundamental prerequisite for its effect, these results promise a good potential of both food supplements for protection against oxidative stress and the consequent cardiovascular risk. [ABSTRACT FROM AUTHOR]

The aim was to identify subgenome‐related specific responses in two types of triticale, that is, of the wheat‐dominated genome (WDG) and rye‐dominated genome (RDG), to water stress induced in the early phase (tillering) of plant growth. Higher activity of the primary metabolism of carbohydrates is a feature of the WDG type, while the dominance of the rye genome is associated with a higher activity of the secondary metabolism of phenolic compounds in the RDG type. The study analyzed carbohydrates and key enzymes of their synthesis, free phenolic compounds and carbohydrate‐related components of the cell wall, monolignols, and shikimic acid (ShA), which is a key link between the primary and secondary metabolism of phenolic compounds. Under water stress, dominance of the wheat genome in the WDG type was manifested by an increased accumulation of the large subunit of Rubisco and sucrose phosphate synthase and a higher content of raffinose and stachyose compared with the RDG type. In dehydrated RDG plants, higher activity of L‐phenylalanine ammonia lyase (PAL) and L‐tyrosine ammonia lyase (TAL), as well as a higher level of ShA, free and cell wall‐bound p‐hydroxybenzoic acid, free homovanillic acid, free sinapic acid, and cell wall‐bound syringic acid can be considered biochemical indicators of the dominance of the rye genome. [ABSTRACT FROM AUTHOR]

The current therapeutic approach for gout is through the inhibition of the xanthine oxidase (XO) enzyme. Allopurinol, a clinically used XO inhibitor, causes many side effects. This study aimed to investigate the interaction between XO and inhibitors identified from Chrysanthemum morifolium by using computational simulation and multispectroscopic methods. The crude extract, petroleum ether, ethyl acetate (EtOAc), and residual fractions were subjected to an XO inhibitory assay and 1H NMR analysis. The EtOAc fraction was shown to be strongly correlated to the XO inhibitory activity by using PLS biplot regression analysis. Kaempferol, apigenin, homovanillic acid, and trans-cinnamic acid were suggested to contribute to the XO inhibitory activity. Molecular docking showed that kaempferol and apigenin bound to the active site of XO with their benzopyran moiety sandwiched between Phe914 and Phe1009, interacting with Thr1010 and Arg880 by hydrogen bonding. Kaempferol showed the lowest binding energy in molecular dynamic simulation. The residues that contributed to the binding energy were Glu802, Arg880, Phe 914, and Phe 1009. A fluorescence quenching study showed a combination of static and dynamic quenching for all four inhibitors binding to XO. Circular dichroism spectroscopy revealed that there was no major change in XO conformation after binding with each inhibitor. [ABSTRACT FROM AUTHOR]

Nilotinib is a tyrosine kinase inhibitor that is safe and tolerated in neurodegeneration, it achieves CSF concentration that is adequate to inhibit discoidin domain receptor (DDR)-1. Nilotinib significantly affects dopamine metabolites, including Homovanillic acid (HVA), resulting in an increase in brain dopamine. HD is a hereditary disease caused by mutations in the Huntingtin's (HTT) gene and characterized by neurodegeneration and motor and behavioral symptoms that are associated with activation of dopamine receptors. We explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients and examined the effects of nilotinib on several brain mechanisms, including dopamine transmission and gene expression via cerebrospinal fluid (CSF) miRNA sequencing. Nilotinib, 150 mg, did not result in any behavioral changes, although it significantly attenuated HVA levels, suggesting reduction of dopamine catabolism. There was no significant change in HTT, phosphorylated neuro-filament and inflammatory markers in the CSF and plasma via immunoassays. Whole miRNA genome sequencing of the CSF revealed significant longitudinal changes in miRNAs that control specific genes associated with autophagy, inflammation, microglial activity and basal ganglia neurotransmitters, including dopamine and serotonin. [ABSTRACT FROM AUTHOR]

BACKGROUND: Clinical collapse in the newborn most often occurs secondary to sepsis, delivery complications, congenital cardiac defects, or inborn errors of metabolism. We report on a neonate with respiratory, cardiac, and hepatic failure, with disproportionate metabolic acidosis and systemic hypertension, found to be caused by a congenital neuroblastoma. CASE DESCRIPTION: A term infant presented to our Level IV NICU via emergent transport at 12 hours of life with clinical and laboratory findings consistent with respiratory, cardiac, and hepatic failure. Typical workup for sepsis and cardiac etiology was unrevealing. The infant was noted to have systemic hypertension despite prolonged capillary refill. A profound metabolic acidosis led the primary team to pursue a genetics consult. In the course of the workup for disorders of metabolism, a urine organic acids panel revealed an elevated HVA (homovanillic acid) and VMA (vanillylmandelic acid), the metabolites of the neurotransmitters epinephrine, norepinephrine and dopamine. Subsequent abdominal ultrasound and chest/abdomen CT revealed a large heterogeneous mass with internal vascular flow and scattered calcifications arising from the medial limb of the left adrenal gland, consistent with neuroblastoma. CONCLUSION: Although rare, neuroblastomas can present clinically in the perinatal period in a manner requiring immediate life-saving intervention. Providers should consider the diagnosis in the setting of a newborn with a sepsis-like syndrome or profound metabolic acidosis presenting along with systemic hypertension without clear underlying etiology. [ABSTRACT FROM AUTHOR]

Neurotransmitter metabolism plays a critical role in the pathophysiology of major depressive disorder (MDD). However, whether the neurotransmitter metabolism in adolescent MDD is differentiated from adult MDD is still elusive. In the current study, plasma concentrations of monoamine and amino acid neurotransmitters as well as their metabolites, including tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), vanillylmandelic acid (VMA), 3-methoxy-4-hydroxyphenylglycol (MHPG), glutamine (GLN), glutamate (GLU) and gamma-aminobutyric acid (GABA), were measured and compared in two cohorts of subjects (adult cohort: 31 first-episode MDD vs. 35 healthy controls; adolescent cohort: 33 first-episode MDD vs. 30 healthy controls). To assess the effects of antidepressant treatment, we also analyzed the concentrations of these indexes pre- and post-treatment in adult and adolescent cohorts. At baseline, the deficits of neurotransmitter metabolism in adult MDD were manifested in all the neurotransmitter systems. In contrast, for adolescent MDD, the dysregulation of neurotransmission was mainly indicated in the catecholaminergic systems. After antidepressant treatment, adult MDD showed increased TRP, KYN, KYNA and GLU levels, together with decreased levels of 5-HIAA and DOPAC. Adolescent MDD illustrated an increased level of 5-HT and decreased levels of TRP and GABA. The improvements of Hamilton total scores correlated with the changes in plasma TRP and the turnover of KYN/TRP after treatment in all MDD patients. However, these correlations were only manifested in the adult MDD rather than in adolescent MDD patients. The findings highlight the shared and distinguished neurotransmitter pathways in MDD and emphasize the different antidepressant responses between adults and adolescents. Potentially, the neurotransmitters above could serve as diagnostic biomarkers and provide a novel pharmacological treatment strategy for MDD. [ABSTRACT FROM AUTHOR]

Background: There has been increasing evidence that exercise therapy is effective in the treatment and prevention of major depression (MD). However, the basic molecular mechanisms underlying the effects of exercise on MD remain unclear. We conducted a preliminary study to clarify the effect of exercise therapy on MD, focusing on the dynamics of nitric oxide (NO) and catecholamine metabolites, which have been found to be associated with MD. Methods: Eleven outpatients with mild to moderate MD and 37 healthy controls (HC) were included in the study. The participants' clinical records and questionnaires were screened for their past medical history. For their exercise therapy, the participants were instructed to walk the equivalent of 17.5 kcal/kg/week for 8 weeks. Blood samples were collected from all participants at baseline, 4 weeks, and 8 weeks after the start of exercise therapy, and plasma metabolites of NO (NOx), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were analyzed. We also assessed the 17-item Hamilton Rating Scale for Depression (HRSD-17) in patients with MD. A mixed-effects regression model was used to compare the mean values by time (baseline, 4, and 8 weeks) for the three corresponding groups (NOx, MHPG, and HVA). Results: HRSD-17 scores decreased significantly in the MD group after 8 weeks of exercise therapy. NOx and MHPG increased, but there was no significant change in HVA in the MD group after the exercise therapy. NOx decreased after exercise, and HVA increased significantly from baseline after 4 weeks of exercise but decreased after 8 weeks of exercise in the HC group. Conclusions: The effects of exercise on NOx, MHPG, and HVA may differ between MD and HC. The potential mechanisms for the benefits of walking exercise in MD patients will be the subject for future research. [ABSTRACT FROM AUTHOR]

Gradient elution for the determination of six selected neurotransmitters (3,4-dihydroxyphenylacetic acid, dopamine, homovanillic acid, 5-hydroxyindole-3-acetic acid, L-noradrenaline, serotonin) by HPLC with fluorescence detection on the C18 reverse phase was designed and optimized. The elution used the binary mobile phase of aqueous solution of 12 × 10−3 mol dm−3 acetic acid, 0.26 × 10−3 mol dm−3 Na2EDTA, pH = 3.5) and methanol. Furthermore, modified homogenization medium, prepared by mixing methanol and an aqueous solution (0.4 mol dm−3 perchloric acid, 6 × 10−3 mol dm−3 cysteine, 1 × 10−3 mol dm−3 L-ascorbic acid, and 0.54 × 10−3 mol dm−3 Na2EDTA) in a ratio of 1:1 (v/v), was introduced in the preparation of rat brain tissue to increase the stability of neurotransmitters in the sample before the analysis. Both developed procedures were successfully applied to the determination of selected neurotransmitters in authentic brain tissue samples from rats affected by morphine and/or morphine abstinence. The statistically significant increases in dopamine, 3,4-dihydroxyphenylacetic acid, and serotonin levels in the striatum, as well as L-noradrenaline in the cerebral cortex of rats affected by intraperitoneal administration of morphine, were measured. [ABSTRACT FROM AUTHOR]

European wild garlic (Allium ursinum L.) syn. wood garlic, ramsons or bear's garlic is a perennial plant that is common in Europe and Asia, but rare in the Mediterranean region. Bear's garlic is included in the Latvian Red Data Book. The plant species has high commercial value and a high amount of biologically active compounds. Because of the conservation status of wild populations, raw material should be obtained by cultivation. For the experiment, leaves of six accessions of bear's garlic from the ex situ collection of medicinal and aromatic plants at the Latvia University of Life Sciences and Technologies, were used. The aim of this study was to identify the individual phenolic compounds in bear's garlic leaves. The composition of the phenolic profile was determined using a high-performance liquid chromatograph (HPLC) Shimadzu Nexera LC-40 with diode-array detector (DAD). Overall, 18 phenolic compounds (gallic acid, 3.5-diOHbenzoic acid, catechin, chlorogenic acid, 4-hydroxybenzoic acid, epicatechin, homovanillic acid, caffeic acid, vanillic acid, syringic acid, vanillin, p-coumaric acid, rutin, sinapic acid, ferulic acid, 2-OHcinnamic acid, quercetin, luteolin, and kaempferol) were detected in the samples. The gallic acid was the predominant phenolic compound, with a range in concentration from 75.8 mg·100 g−1 to 322.5 mg·100 g−1 in bear's garlic. [ABSTRACT FROM AUTHOR]

Volatile profiles of unifloral honeys and meads prepared in different ways (boiled-saturated, not boiled-unsaturated) were investigated by headspace solid-phase micro extraction (HS-SPME) and dehydration homogeneous liquid–liquid extraction (DHLLE) followed by GC-FID/MS analyses. The obtained data were analyzed by principal component analysis (PCA) to evaluate the differences between the investigated products. The volatile profiles of honey as well as the boiled and the not boiled meads prepared from it showed significant discrepancies. The meads contained more aliphatic acids and esters but fewer monoterpenes and aliphatic hydrocarbons than the honey. Significant/substantial differences were found between the boiled (more aliphatic alcohols and acids) and the not boiled meads (more aliphatic hydrocarbons and esters). Some compounds related to yeast metabolism, such as tryptophol, may be considered markers of honey fermentation. This research allowed us to identify chemical markers of botanical origin, retained and detectable in the meads: 4-isopropenylcyclohexa-1,3-diene-1-carboxylic acid and 4-(1-hydroxy-2-propanyl)cyclohexa-1,3-diene-1-carboxylic acid for linden; valeric acid, γ-valerolactone, p-hydroxybenzoic acid for buckwheat; 4-hydroxybenzeneacetic acid, homovanillic acid and trans-coniferyl alcohol for honeydew; and methyl syringate for canola. [ABSTRACT FROM AUTHOR]

The phytochemical profiles of fermented barley with Lactiplantibacillus plantarum dy-1 (LFBE) and its antioxidant activity were investigated. Nine components including cinnamaldehyde, homovanillic acid, coumalic acid, quercetin, docosahexaenoic acid methyl ester, gallic acid, cafestol, 6-hydroxycaproic acid, and indole-3-lactic acid were identified by HPLC-MS/MS and evaluated as potential antioxidants in LFBE. DPPH and ABTS scavenging ability, superoxide dismutase (SOD) activity, reactive oxygen species (ROS) level in HepG2 cells, and the cellular antioxidant activity (CAA) were assessed. The results indicated that the nine components showed good radical scavenging capacities, most of them had the abilities of reducing ROS level and promoting SOD activity. In CAA tests, coumalic acid exhibited the highest value (11.51 μmol of QE/100 g), while gallic acid showed the lowest value (3.47 μmol of QE/100 g), which was not consistent with the trend of other evaluations. This study provided a basis for understanding the effects of fermentation on bioactivity of barley. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorders (ASD) are characterized by numerous comorbidities, including various metabolic and nutritional abnormalities. In many children with ASD, problems with proper nutrition can often lead to inadequate nutrient intake and some disturbances in metabolic profiles, which subsequently correlate with impaired neurobehavioural function. The purpose of this study was to investigate and compare the relationship between supplementation, levels of homovanillic acid (HVA) and vanillylmandelic acid (VMA) and the behaviour of children with ASD using quantitative urinary acid determination and questionnaires provided by parents/caregivers. The study was carried out on 129 children between 3 and 18 years of age. HVA and VMA were extracted and derivatized from urinary samples and simultaneously analyzed by gas chromatography-mass spectrometry (GC-MS). In addition, parents/caregivers of children with ASD were asked to complete questionnaires containing information about their diet and intake/non-intake of supplements. The application of the Mann–Whitney U test showed a statistically significant difference between the level of HVA and vitamin B supplementation (p = 1.64 × 10−2) and also omega-6 fatty acids supplementation and the levels of HVA (p = 1.50 × 10−3) and VMA (p = 2.50 × 10−3). In some children, a reduction in the severity of autistic symptoms (better response to own name or better reaction to change) was also observed. These results suggest that supplementation affects the levels of HVA and VMA and might also affect the children's behaviour. Further research on these metabolites and the effects of supplementation on their levels, as well as the effects on the behaviour and physical symptoms among children with ASD is needed. [ABSTRACT FROM AUTHOR]

The aim of this study was to reveal whether increased reward dependence (RD) plays a role in the catecholamine neurotransmitter release and testosterone hormone regulation during physical activities among healthy trained participants. Twenty-two male participants (mean age: 40.27 ± 5.4 years) participated in this study. Two conditions were constructed, namely, a noncompetitive and a competitive running task (RT), which were separated by a 2-week interval. Urine and blood samples were collected prior to and following the running tasks. Noradrenaline (NA), adrenaline (A), dopamine (D), and their metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA), were measured from urine, while testosterone levels were analyzed from blood samples. RD was assessed using the Cloninger's Personality Inventory (PI). Mental health was evaluated using the WHO Well-Being, Beck Depression, and Perceived Life Stress Questionnaires. According to our findings, levels of NA, A, D, VMA, and testosterone released underwent an increase following physical exertion, independently from the competitive condition of the RT, while HVA levels experienced a decrease. However, we found that testosterone levels showed a significantly lower tendency to elevate in the competitive RT, compared with the noncompetitive condition (p = 0.02). In contrast, HVA values were higher in the competitive compared with the noncompetitive condition (p = 0.031), both before and after the exercise. Considering the factor RD, in noncompetitive RT, its higher values were associated with elevated NA levels (p = 0.007); however, this correlation could not be detected during the competitive condition (p = 0.233). Among male runners, the NA and testosterone levels could be predicted to the degree of RD by analyzing competitive and noncompetitive physical exercises. [ABSTRACT FROM AUTHOR]

Prepartum exercise (PA) has been proposed as a strategy for the peripartum management of dairy cows; however, the mechanism by which PA affects metabolism has not been elucidated. Here, we investigated the metabolic changes in transition dairy cows with PA. Holstein transition multiparous dairy cows were assigned to an exercise (n = 12) or a control (n = 12) group; the cows in the exercise group walked for a targeted 45 min at 3.25 km/h, two times a day. Plasma non-esterified fatty acid (NEFA), β-hydroxybutyric acid (BHBA), glucose, and triglyceride levels were measured, and metabolic profiles were analyzed using untargeted mass spectrometry. Compared with those in the control group, the concentrations of NEFA at −7 d, glucose at 0 d, and BHBA at +7 d relative to calving were considerably decreased in the exercise group. Untargeted metabolomics analysis revealed differences in the levels of key metabolites, including kynurenine, tryptophan, homovanillic acid, dopamine, cis-9-palmitoleic acid, and palmitic acid, between the exercise and control group cows. This study suggests that PA may decrease homovanillic acid and cis-9-palmitoleic acid levels and increase tryptophan levels to alleviate the metabolic stress in dairy cows during calving, thereby improving postpartum health. [ABSTRACT FROM AUTHOR]